Cancer patients receiving cytotoxic antineoplastic therapy sufficient to adversely affect myelopoiesis and the developmental integrity of the gastrointestinal mucosa are at risk for invasive infection due to colonizing bacteria and/or fungi that translocate across intestinal mucosal surfaces. Since the magnitude of the neutrophil-mediated component of the inflammatory response may be muted in neutropenic patients [1], a fever may be the earliest and only sign of infection. It is critical to recognize neutropenic fever early and to initiate empiric systemic antibacterial therapy promptly in order to avoid progression to a sepsis syndrome and possibly death.

Guidelines have been developed for the evaluation and management of fever in neutropenic patients with cancer [2,3]. The recommendations below are generally in keeping with the 2010 Infectious Diseases Society of America (IDSA) guidelines [2] and the 2013 American Society of Clinical Oncology (ASCO) guidelines [4]. (See 'Society guideline links' below.)

DEFINITIONS

Fever — The definition of fever as an indicator of infection in neutropenic patients has varied. In 1868, Carl Wunderlich proposed that the mean normal body temperature was 37°C (98.6°F) with an upper limit of normal of 38°C (100.4°F), above which fever was defined [5-7]. Despite the observation that there is a range of normal body temperatures, in one survey, a majority (75 percent) of 270 medical professionals reported the belief that normal body temperature is 37°C (98.6°F) [7,8]. A survey of members of the British Society for Haematology regarding their institutional definitions of fever identified 10 definitions of fever, ranging from a single temperature >37.5°C to either a single temperature >39°C or two successive temperatures >38.4°C [9]. These beliefs notwithstanding, the empirically observed mean oral temperature of 148 healthy adults between ages 18 and 40 years was reported as 36.8±0.4°C (98.2±0.7°F) with a range of 35.6°C (96.0°F) to 38.2°C (100.8°F), the latter defining the upper limit of normal [6].

The Infectious Diseases Society of America defines fever in neutropenic patients as a single oral temperature of ≥38.3°C (101°F) or a temperature of ≥38.0°C (100.4°F) sustained over a one-hour period [2]. We agree with using this definition of fever in neutropenic patients. Similar definitions have been provided from South America, Europe, and Asia [10-12].

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US Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Common terminology criteria for adverse events (CTCAE). http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf (Accessed on February 16, 2012).